It's all in the genes

Steamboat company looks to profit from breakthrough in measuring genetic activity

Steamboat Springs  A biotech company based in Steamboat Springs is the sole marketer of a product that promises to better predict and treat disease by using a person's genetic fingerprint.

The 10-year-old company, Gene Express Inc., has yet to make a profit. But now that demand for its product and international attention are increasing, owners said the company has huge potential.

Al Pollock, a longtime Steamboat resident and CEO of the company, said he thinks that in the next two years, Gene Express could gain 1 percent of a $3 billion gene expression market, and could become the Microsoft of the biotech industry.

"We'll be the toolmakers and we'll supply this tool for everyone else to use," the 56-year-old Pollock said. "It's sort of like Microsoft. All they have to do is focus on that program, and as long as everybody uses their program, they don't care who makes the computer, or who makes the chip."

The tool that Gene Express supplies is a sort of ruler for the molecular world.

Most scientific research depends on a standard unit of measurement. Weight, length, and temperature are all measured with standard units such as a pound, an inch, and a degree.

But there was no standard unit of measurement for determining how active a gene or a section of DNA is inside a cell until Gene Express' chief scientist Dr. Jim Willey of Toledo, Ohio invented one 10 years ago.

"What if everybody were trying to build a house and no one had a constant unit of measurement? It'd be very expensive and difficult," said Willey, who is part owner of Gene Express and also a researcher, medical doctor and professor at the Medical College of Ohio. "(Our tool) is going to allow everything in molecular biology to move faster."

The tool's name is StaRT-PCR, an abbreviation for the mouthful "standardized reverse transcriptase polymerase chain reaction," which describes the process.

Because of patent protection, Gene Express will be the only supplier of the materials needed for StaRT-PCR. Pollock is now appearing at research symposiums and increasing publicity in order to get the word out about the technology.

Both Pollock and Willey said that there is a lot to be gained financially, but that they aren't focused on the earnings.

Pollock said he's just excited to be involved in groundbreaking research.

"I'm not looking at the gold at the end of the rainbow. I believe it's there," Pollock said. "But (the research) is where our hearts are. This is going to impact society for the future in terms of the quality of our lives."

Chance beginning

Pollock, who has worked as a math teacher and a real estate broker, taught and coached Willey in high school in Ohio. The pair met up again in 1992 through friends and family, and Willey described his new technology to Pollock.

Pollock said he didn't give the research much thought at first, but a few months later, he had a change of mind and tracked Willey down to find out more.

Soon Pollock found himself pulled into a partnership with Willey, in which Willey focuses on research and Pollock takes care of the business.

Pollock's work includes obtaining patents for the technology, marketing and promoting the company's products, and encouraging investors to support the company.

Although Willey's research is based in Toledo, Pollock decided to work out of his home in downtown Steamboat because he has lived in the area since 1973.

Pollock tries to keep much of the operation local: one of his accountants is also in Steamboat, and the company's board of directors is composed of two of his friends. So far, Pollock has funded the company mostly through the support of friends and family.

Now, Pollock talks in terms of cells and mRNA, and jumps on any opportunity to explain why StaRT-PCR is superior to other methods of measuring gene expression.

How it works

Here's how StaRT-PCR works.

A cell's DNA contains bits of information or genes on how to make proteins in the cell. Before making the proteins, the cell copies the information in a gene into a strand of mRNA, which serves as a set of instructions.

The number of strands of mRNA from a certain gene represents how active that gene is. StaRT-PCR counts these mRNA strands, and so measures gene activity.

This measurement is important, as cancers and other diseases are often caused by genes that are too active or are not active enough.

To count the mRNA using StaRT-PCR, researchers take a sample of a person's cells and mix it with what they call an "internal standard." The standard is a piece of DNA that is similar to the gene they are measuring but shorter.

Then researchers put this mixture through a process called PCR, which copies the gene and the standard at the same rate. At the end, they count how many copies of each they have, and because they know how much of the standard was present at the beginning, they can figure out how much mRNA was in the cell.

With this process, Willey said that researchers can learn the basics of how the human body works, which groups of genes cause diseases, and which types of diseases will respond to treatment.

The technique already has several important uses.

n Researchers can diagnose the 20 percent of lung cancer cases that other tests usually miss by swiping a person's lungs with a wire brush to collect cells and then using StaRT-PCR to measure expression of three genes.

n Researchers can also predict which heavy smokers will get lung cancer by measuring the expression of six genes, a process that takes less time and money than current screening practices.

n And, researchers can quickly determine if a woman suffering from breast cancer will respond to chemotherapy, or if she has a form of cancer that won't respond to the treatment.

Changing medicine

Pollock said that this technology is changing medicine for the better.

"I think this is a whole new way of looking at health issues. Up to this point, we've waited until someone gets sick and we try to treat them in a merciful way," Pollock said. "This is going to try to prevent disease before it happens."

The company's research center moved from Huntsville, Ala., to Toledo in March after receiving a $1 million grant from the National Cancer Institute. The grant will be used to set up a production station to measure gene expression in samples that researchers send in from all over the world.

Conducting research

Once there is more demand than that station can handle, Gene Express will build another production station that will provide the same services for the same prices.

For now, the company sells testing kits to researchers who want to measure gene expression. The kits are small plastic boxes filled with test tubes, with each tube holding less than a drop of liquid with the snippets of genes and materials needed for the test.

So far, StaRT-PCR can be used to measure about 400 genes. In two years, the company plans to be able to measure the 10,000 to 12,000 human genes that have clinical, scientific or commercial significance. The whole human genome has about three or four times that many genes.

Not a new concept

Measuring gene expression is not a new concept. There are two other important methods: Microarray technology and Real-Time PCR.

But, Pollock and Willey said that the StaRT-PCR technique is superior to the competition.

For starters, StaRT-PCR is standardized, which means that it gives an actual measurement of gene expression and not just a relative value. That way, researchers in different laboratories all over the country will be able to compare and combine notes.

Also, StaRT-PCR is inexpensive, only needs a small cell sample and can measure the expression of many genes at once.

Other researchers in the gene expression field agreed that it looks like StaRT-PCR could be the future for gene expression technology.

"I realized that when it comes to (measuring gene expression), one was going to have to work with very small number of cells," said Dr. Bill Thilly, who is a professor of biological engineering at the Massachusetts Institute of Technology. "As far as I can tell, Willey's technology is the only one at this point and time that's capable of playing that game."

The competition

Although many researchers and companies have invested heavily in the other technologies, Willey said there have already been some shifts to using StaRT-PCR.

"None of those companies are going to be eager to have some company that originated in Toledo, Ohio and Steamboat Springs become the standard for gene expression," Willey said. "But my guess is that that's what's going to happen."

Pollock said that in some respects, these larger companies have been helpful for Gene Express.

"They got everybody interested in measuring gene expression," Pollock said. "Now what I have to do is convince them that my tool is so much better, and that's happening fairly quickly."

Mastering the science

Although Pollock was not experienced in the molecular science behind the technique, Willey said he has picked it up fast, and has used his business skills well.

"Al's got a lot of business expertise," Willey said. "He's got a very good understanding of how to develop something over a period of time and to maintain good control over the situation so it's not oversold."

For Pollock, picking the science up is easy because he said he finds it fascinating.

"It's like a whole new frontier. This is a whole leap looking at everything from a genetic level," he said. "The more I got into it, it just drew me in."